Meproadifen enhances activation and desensitization of the acetylcholine receptor‐ionic channel complex (AChR): single channel studies

Abstract

The effects of the quaternary agent meproadifen on ACh-activated channel currents were studied on myoballs cultured from hind limb muscles of neonatal rats. Meproadifen (0.02–0.1 μM) combined with ACh (0.1–0.3 μM) in the patch pipette caused an increase, followed by a decrease, in the frequency of channel openings. At concentrations greater than 0.2 μM the initial phase was not detected and a rapid and marked reduction in the opening frequency was observed. Meproadifen (up to 2.5 μM) produced no change in the duration or conductance of the open state of ACh-activated channels. In addition, this agent induced the appearance of events with a marked increase in the ‘noise’ during the opening phase. The lack of effect under inside-out patch conditions suggested that meproadifen binds to a site located at the external portion of the nicotinic macromolecule and has no access to it through the cell membrane. This study indicated that non-competitive antagonists such as meproadifen can facilitate receptor activation and desensitization.MeproadifenNicotinic acetylcholine receptorSingle channel currentEndplate regionActivation-desensitizatio